Throughout this application, various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citation for these references may be found at the end of this application, preceding the claims.
The photophysics of octahedral 4d6 and 5d6 coordination complexes has been studied extensively. These coordination complexes, particularly those prepared with Ru and Os, have been used in a variety of photonic applications, including photocatalysis and photoelectrochemistry. More recently, researches have investigated the photophysics of isoelectronic Rh3+ and Ir3+ complexes, with both diimine and cyclometallated ligands, such as 2-phenylpyridinato-C2,N (ppy). The cyclometallated ligands are formally monoanionic and can thus be used to prepare neutral tris-ligand complexes, which are isoelectronic with the cationic trisdiimine complexes of Ru and Os, e.g., fac-M(ppy)3, fac-M(2(α-thiophenyl)-pyridine)3 (fac=facial). The d6 Ir complexes show intense phosphorescence at room temperature, while the Rh complexes give measurable emission only at low temperatures.
Recently, the chemistry of cyclometallated Ir(III) complexes has received a great deal of attention. These complexes have proven to be very efficient emissive dopants in molecular and polymeric light emitting diodes (1). For example, efficient multilayer devices with Irppy doped into a hole transporting polymer layer have been reported (14). Heavy metal complexes, particularly those containing Pt and Ir, can serve as efficient phosphors in organic light emitting devices. In these devices, holes and electrons are injected into opposite surfaces of a planar multiplayer organic thin film. The holes and electrons migrate through the thin film to a material interface, where they recombine to form radiated excited states, or excitons. This electrically generated exciton can be either a singlet or a triplet. Both theoretical predictions and experimental measurements give a singlet/triplet ratio for these excitons of 1 to 3. Fluorescent materials typically used to fabricate organic light emitting diodes (OLEDs) do not give detectable triplet emission (i.e., phosphorescence), nor is there evidence for significant intersystem crossing between the triplet and singlet manifolds at room temperature. The singlet/triple ratio thus implies a limitation of 25% for the internal quantum efficiency for OLEDs based on fluorescence. Strong spin orbit coupling of the metal ion in these OLED phosphors leads to efficient emission from a predominantly triplet excited state, which emits with a long radiative lifetime relative to fluorescent materials (phosphor lifetime=microseconds, fluorescent lifetime=nanoseconds), leading to efficient utilization of both singlet and triplet excitons. The long lifetimes in these phosphors are very useful for efficiently utilizing the excited state energy.
Photodynamic therapy (“PDT”) is a new modality for the treatment of malignancies, diseased tissue or cells, hyperproliferating tissues, pathogens or unwanted normal tissues. Photodynamic therapy (PDT) is the use of an agent such as a photosensitizer, given orally, intravenously, or topically, that can be activated or energized by light. The photoactivating light excites the photosensitizer which, in turn, interacts with oxygen causing the production of the cytotoxic singlet oxygen species. The role of the photosensitizer in the production of singlet oxygen, i.e., that of a molecule which absorbs the incident light energy and transfers it to ground state oxygen, thereby elevating it to its singlet excited state which is the reactive intermediate. The interaction of the cytotoxic oxygen species with tissues in which the photosensitizer is localized causes a modification of the tissue, resulting in a desired clinical effect. Thus, photodynamic therapy involves the application of a photosensitive (photochemotherapeutic) agent either systemically or locally to an affected area of the body, followed by exposure of the photosensitive agent to light of a suitable wavelength to activate the photosensitive agent, whereby the affected cells are killed or their proliferative potential is diminished. The tissue specificity of the resultant phototoxic damage is determined largely, although not entirely, by the relative concentrations of the photosensitizer in each tissue at the time of its exposure to the photoactivating light.
Following systemic administration, many photosensitizers accumulate to varying degrees within tissues depending on the pharmacokinetic and distribution profile of the photosensitizing compound and the cell types comprising the tissues. The chemical factors that enable certain photosensitizers to accumulate to a greater degree at a target site than other photosensitizers is not well understood. Indeed, the biological factors that result in the preferential uptake of some photosensitizers in certain tissue types compared to other tissue types are not well understood either. It is clear, however, that each photosensitizer has its own distribution and pharmacokinetic properties within different tissues and these properties determine the relative usefulness of the photosensitizer for the desired therapy. Currently, rigorous screening and biological evaluation in appropriate model systems is required to identify suitable photosensitizers that display the characteristics necessary to effect a therapy within the diseased or target tissues. One critical problem that has not been addressed however is the differential uptake of the photosensitizer by the target cells relative to the other, normal, cells. Indeed, it is known that uptake is generally a function of the molecular structure of the dye being absorbed and that this property varies with different cell types.
It would therefore be highly desirable to be provided with a series of new photosensitizers that can be easily attached to side groups of histidine, other amino acids, and other biomolecules for use as selective photooxidizing agents for biological materials.
Waste water treatment is usually divided into three stages: primary, the removal of settleable solids; secondary, the removal of readily biodegradable contaminates; and tertiary treatment. Tertiary treatment is, generally, the further treatment of waste water after prior treatment has reduced the chemical oxygen demand (COD) to less than about 60 mg/L and the biochemical oxygen demand (BOD) to less than about 20 mg/L. It may also include the removal of disease causing agents, plant nutrients, synthetic organic chemicals, inorganic chemicals, heat, sediments and radioactive substances. Tertiary treatment processes include lime (or other chemical) clarification, filtration, activated carbon adsorption, and ozone treatment. Ozone (O3), which is the most well known tertiary treatment method, is extremely valuable from an environmental point of view. The process oxidizes organic materials in an aqueous environment producing compounds which do not upset the normal biological equilibrium. Unfortunately, this process is expensive, requiring the initial construction of the plant followed by continued use of electricity and oxygen for its operation. U.S. Pat. No. 4,104,204 describes a process for treating aqueous waste effluents containing organic materials which comprises adding to said aqueous effluents in the presence of oxygen, a water insoluble polymer-based photosensitizer and then photolyzing the resulting suspension with light having wavelengths between 320 nm and about 800 nm.